Composition and method for preventing fouling in (meth)acrylic acid processes

1. A compound having the formula:

Ar—(F)—(E)—(CR 3 R 4 )—(CHR 5 ) m —(T)—(Q)—Ar 1 ,

wherein

T is

 where R 6 is taken together with one of R 7 and R 8 to form a bridge of one to two bridgehead carbon atoms, and the other of R 7 and R 8 is selected from hydrogen and R 9 ;

Ar and Ar 1 are, each phenyl;

F is alkylene, alkenylene, or a bond;

E is selected from —C(═O)N(R 10 )—, —SO 2 N(R 10 )—, —N(R 11 )C(═O)N(R 10 )—, —N(R 11 )SO 2 N(R 10 )—, —N(R 11 )C(—S)N(R 10 )—, —N(R 11 )C(═O)—, —N(R 11 )SO 2 —, —N(R 12 )C(═O)CH(R 13 )—, and CH(R 13 )C(═O)N(R 12 )—, where:

R 10 , R 11 , R 12 , and R 13 are, independently of each other, hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocycloalkyl, heteroalkyl, or -(alkylene)-C(═O)-Z, where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy, or heteroaralkyloxy;

or alternatively, R 12 and R 13 may be taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form a heterocyclyl or heteroaryl ring optionally substituted with up to two groups selected from R 14 ;

R 3 and R 4 are, independently of each other, hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heteroalkyl, -(alkylene)-C(═O)-Z 1 , or -(alkylene)-C(O) 2 Z 1 , where Z 1 is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy, or heteroaralkyloxy;

R 5 is hydrogen or alkyl;

Q is —C(═O)—or C 1-2 alkylene;

R 9 is attached to any available carbon atom of ring T and is selected from lower alkyl, hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, trifluoromethoxy, or a lower alkyl substituted with one of hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, or trifluoromethoxy;

R 14 is selected from lower alkyl, hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, trifluoromethoxy, and a lower alkyl substituted with one of hydroxy, lower alkoxy, halo, cyano, trifluoromethyl, or trifluoromethoxy;

m is 0 or 1; and

n is 0 to 4; and

pharmaceutically acceptable salts thereof.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ar and Ar 1 are both phenyl;

F is a bond;

E is selected from —C(═O)N(R 10 )—, —N(R 11 )C(═O)N(R 10 )—, —N(R 11 )C(═O)—, —N(R 12 )C(—O)CH(R 13 )—, and CH(R 13 )C(═O)N(R 12 )—, where:

R 10 , R 11 , R 12 , and R 13 are, independently of each other, hydrogen or alkyl;

or alternatively, R 12 and R 13 may be taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form a heterocyclyl or heteroaryl ring optionally substituted with up to two groups selected from R 14;

R 3 and R 4 are, independently of each other, hydrogen, alkyl, alkenyl, haloalkyl, heteroalkyl, or -(alkylene)-C(═O)-Z 1 , where Z 1 is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, ammo, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy, or heteroaralkyloxy;

Q —CH 2 —;

R 9 and R 14 are independently selected from methyl, ethyl, hydroxy, methoxy, halo, cyano, trifluoromethyl, or trifluoromethoxy; and

n is 0 to 2.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein T is selected from the group consisting of:

and R 9 is any available carbon atom of ring T and is selected from lower alkyl and hydroxy, and n is 0 to 2.

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ar is a phenyl ring optionally substituted with one, two or three substituents selected from alkyl, heteroalkyl, alkoxy, —COR 15, —SO 2 R 17, methylenedioxy, hydroxy, halo, acylamino, amino, mono- or disubstituted amino, —CONR 15 R 16, -(alkylene)-CONR 15 R 16 , —COOR 15, -(alkylene)-COOR 15 and/or —NR 16 SO 2 R 17 ;

R 15 and R 16 are each independently hydrogen or alkyl; and

R 17 is alkyl, amino or mono or disubstituted amino.

5. A compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein

Ar is selected from phenyl, 4-chlorophenyl, 4-methylphenyl, 4-methoxyphenyl, 3-methylsulfonylphenyl, 3,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, and 3,4,5-trimethoxyphenyl.

6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein F is a bond.

7. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

E is —C(═O)N(R 10 )—, —N(R 10 )C(═O)N(R 11 )—, or N(R 12 )C(═O)CH(R 13 )—, where R 10 and R 11 are hydrogen or lower alkyl, and R 12 and R 13 are taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form

 where R 18 and R 19 are selected from hydrogen and lower alkyl.

8. A compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein

E is

 and m is 0.

9. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R 3 is hydrogen; and

R 4 is hydrogen, methyl, ethyl, 1-methylethyl, isopropyl, 1-hydroxyethyl or 2-hydroxyethyl.

10. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R 3 is hydrogen; and R 4 is 1-methylethyl.

11. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein T is

12. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q is —CH 2 —.

13. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ar 1 is a phenyl ring optionally substituted with one, two or three substituent selected from alkyl, heteroalkyl, alkoxy, halo, trifluoromethyl, nitro, or mono- or disubstituted amino.

14. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ar 1 is 4-chlorophenyl or 3,4-dichlorophenyl.

15. A compound having the formula (II):

or a pharmaceutically-acceptable salt thereof, in which:

T is

 where R 6 is taken together with one of R 7 and R 8 to form a bridge one to two bridgehead carbon atoms optionally substituted with one to two CH 3 , and the other of R 7 and R 8 is selected from hydrogen and lower alkyl;

E is selected from —C(═O)N(R 10 )—, —N(R 11 )C(—O)N(R 10 )—, and —N(R 12 )C(═O)CH(R 13 )—, where:

R 10 , R 11 , R 12 , and R 13 are independently of each other hydrogen or lower alkyl, or alternatively, R 12 and R 13 may be taken together with the nitrogen and carbon atoms to which they are attached, respectively, to form a five-membered heterocyclyl or heteroaryl ring having up to two N atoms and optionally substituted with up to two groups selected from methyl, ethyl, hydroxy, methoxy, halo, cyano, trifluoromethyl, and trifluoromethoxy;

R 4 is hydrogen, lower alkyl, or lower alkyl substituted with hydroxy;

R 20 and R 21 are each independently selected from halo, OR 22 , and SO 2 R 22 , wherein R 22 is lower alkyl;

is 0 or 1;

p and q are independently 0, 1, 2 or 3.

16. A compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein

E is selected from —C(═O)NH—, —NHC(═O)NH—, and

 where R 18 and R 19 are each hydrogen or lower alkyl;

R 4 is hydrogen, methyl, ethyl, 1-hydroxyethyl, or 1-methylethyl;

R 6 is taken together with one of R 7 and R 8 to form a bridge of two bridgehead carbon atoms and the other of R 7 and R 8 is hydrogen;

R 20 is selected from halo, methoxy, and methylsulfonyl;

R 21 is halo;

p is 0, 1, 2 or 3; and

q is 0, 1, or 2.

17. A compound of claim 16 , or a pharmaceutically acceptable salt wherein T is